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Cancer represents a major public health issue and a primary cause of death for the mankind and the search for alternative cancer treatments that assist or alleviate the drawbacks of current cancer therapies remains imperative. Nanocatalytic medicine represents a new discipline that aims at exploiting the unique response of heterogeneous catalysts exposed to unconventional conditions such as those encountered in the tumor microenvironment (TME). Photo-triggered cancer therapies using light-activable catalytic materiales can stimulate and activate multiple biological processes and represent a very promising field of study. Herein, we evaluate the use of carbon nanodots with different composition (CNDs) retrieved by laser pyrolysis as potential near-infrared (NIR) photosensitizers able to activate P25 semiconductor nanostructured photocatalysts. We describe the enhanced photocatalytic response towards glucose conversion and reactive oxygen species (ROS) generation upon irradiation with NIR-LEDs when CNDs doped with heteroatoms were tested. The most active photocatalysts were evaluated in the presence of cancer cells and revealed a promising photodynamic effect under NIR irradiation. This work represents one of the scarce examples of a conventional inorganic photocatalyst containing TiO2 that is translated into a biomedical application with a successful outcome.

Platinum nanoparticles (Pt NPs) have a well-established role as a classic heterogeneous catalyst. Also, Pt has traditionally been employed as a component of organometallic drug formulations for chemotherapy. However, a new role in cancer therapy is emerging thanks to its outstanding catalytic properties, enabling novel approaches that are surveyed in this review. Herein, we critically discuss results already obtained and attempt to ascertain future perspectives for Pt NPs as catalysts able to modify key processes taking place in the tumour microenvironment (TME). In addition, we explore relevant parameters affecting the cytotoxicity, biodistribution and clearance of Pt nanosystems. We also analyze pros and cons in terms of biocompatibility and potential synergies that emerge from combining the catalytic capabilities of Pt with other agents such as co-catalysts, external energy sources (near-infrared light, X-ray, electric currents) and conventional therapies., The authors gratefully acknowledge funding from the European Commission (ERC Advanced Grant-742684 CADENCE).

The use of inorganic nanomaterials to tackle and exploit the intrinsic chemical nature of the tumor microenvironment (TME) has emerged as a promising strategy in cancer therapy. Manganese oxide nanoparticles (MnxOy) offer unique advantages in terms of redox properties and specificity towards the TME scenario: low O2 concentrations, mildly acidic pH and high oxidative stress; environmental conditions that often lead to a reduction in the efficacy of cancer treatments. MnxOy-based nanoplatforms have recently demonstrated exciting properties as inorganic nanocatalysts to operate under TME constraints. Alternatively, Mn-nanocatalysts have also displayed synergistic anticancer response in combination with other active co-adjuvant elements (drugs, enzymes or nanomaterials). The aim of this review is to provide new insights on the main functionalities of Mn-based nanomaterials applied to cancer therapy. We analyze its capacity as oxygen supplier in hypoxic scenarios, its role to induce the selective depletion of glutathione (GSH) to maximize cell stress or its capacity to promote starvation therapy via glucose oxidation. We aim at providing an insightful view of the operating mechanisms behind each of these critical processes and highlight the versatility and catalytic richness of Mn-based nanoparticles in this developing field. We also provide a general and comprehensive analysis of the Mn fate when trafficking through the intracellular levels., Financial support from the European Research Council (ERC Advanced Grant CADENCE number 742684) is gratefully acknowledged. J.B-A. thanks the Spanish Government for an FPU predoctoral contract.

Heterogeneous catalysis has emerged as a promising alternative for the development of new cancer therapies. In addition, regarding the tumor microenvironment as a reactor with very specific chemical features has provided a new perspective in the search for catalytic nanoarchitectures with specific action against chemical species playing a key role in tumor metabolism. One of these species is glutathione (GSH), whose depletion is the cornerstone of emerging strategies in oncology, since this metabolite plays a pivotal regulatory role as antioxidant agent, dampening the harmful effects of intracellular reactive oxidative species (ROS). Herein, we present copper-iron oxide spinel nanoparticles that exhibit a versatile and selective catalytic response to reduce GSH levels while generating ROS in a cascade reaction. We demonstrate a clear correlation between GSH depletion and apoptotic cell death in tumor cells in the presence of the copper-iron nanocatalyst. Furthermore, we also provide a novel analytical protocol, alternative to state-of-the-art commercial kits, to accurately monitoring the concentration of GSH intracellular levels in both tumor and healthy cells. We observe a selective action of the nanoparticles, with lower toxicity in healthy cell lines, whose intrinsic GSH levels are lower, and intense apoptosis in tumor cells accompanied by a fast reduction of GSH levels., Financial support from the European Research Council (ERC-Advanced Grant CADENCE number 742684) is gratefully acknowledged. The TEM measurements were conducted at the Laboratorio de Microscopias Avanzadas, Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Spain. The synthesis of materials has been performed by the Platform of Production of Biomaterials and Nanoparticles of the NANBIOSIS ICTS, more specifically by the Nanoparticle Synthesis Unit of the CIBER in BioEngineering, Biomaterials & Nanomedicine (CIBER-BBN). J.B-A. acknowledges the Spanish Government for an FPU predoctoral contract. We would also like to thank to the Scientific Services of the Aragon Institute of Health Sciences (IACS), specifically to the Cell culture, Microscopy, and Citometry Services and their specialist and the ICTS ELECMI.

This article belongs to the Special Issue 10th Anniversary of Catalysts—Feature Papers in Photocatalysis., The present review aims at highlighting recent advances in the development of photocatalysts devoted to cancer therapy applications. We pay especial attention to the engineering aspects of different nanomaterials including inorganic semiconductors, organic-based nanostructures, noble metal-based systems or synergistic hybrid heterostructures. Furthermore, we also explore and correlate structural and optical properties with their photocatalytic capability to successfully performing in cancer-related therapies. We have made an especial emphasis to introduce current alternatives to organic photosensitizers (PSs) in photodynamic therapy (PDT), where the effective generation of reactive oxidative species (ROS) is pivotal to boost the efficacy of the treatment. We also overview current efforts in other photocatalytic strategies to tackle cancer based on photothermal treatment, starvation therapy, oxidative stress unbalance via glutathione (GSH) depletion, biorthogonal catalysis or local relief of hypoxic conditions in tumor microenvironments (TME)., This research was funded by the European Research Council (ERC) through an Advanced Research Grant (CADENCE, grant number 742684). J.B.-A. acknowledges the Spanish Government for a PhD predoctoral grant (FPU18/04618). J.I.G.-P. thanks the Regional Government of Aragon (DGA) for granting a PhD predoctoral contract.

The present work sheds light on a generally overlooked issue in the emerging field of bio-orthogonal catalysis within tumour microenvironments (TMEs): the interplay between homogeneous and heterogeneous catalytic processes. In most cases, previous works dealing with nanoparticle-based catalysis in the TME focus on the effects obtained (e.g. tumour cell death) and attribute the results to heterogeneous processes alone. The specific mechanisms are rarely substantiated and, furthermore, the possibility of a significant contribution of homogeneous processes by leached species – and the complexes that they may form with biomolecules – is neither contemplated nor pursued. Herein, we have designed a bimetallic catalyst nanoparticle containing Cu and Fe species and we have been able to describe the whole picture in a more complex scenario where both homogeneous and heterogeneous processes are coupled and fostered under TME relevant chemical conditions. We investigate the preferential leaching of Cu ions in the presence of a TME overexpressed biomolecule such as glutathione (GSH). We demonstrate that these homogeneous processes initiated by the released by Cu–GSH interactions are in fact responsible for the greater part of the cell death effects found (GSH, a scavenger of reactive oxygen species, is depleted and highly active superoxide anions are generated in the same catalytic cycle). The remaining solid CuFe nanoparticle becomes an active catalyst to supply oxygen from oxygen reduced species, such as superoxide anions (by-product from GSH oxidation) and hydrogen peroxide, another species that is enriched in the TME. This activity is essential to sustain the homogeneous catalytic cycle in the oxygen-deprived tumour microenvironment. The combined heterogeneous–homogeneous mechanisms revealed themselves as highly efficient in selectively killing cancer cells, due to their higher GSH levels compared to healthy cell lines., Financial support from the European Research Council (ERC Advanced Grant CADENCE number 742684) is gratefully acknowledged. The TEM measurements were conducted at the Laboratorio de Microscopias Avanzadas, Instituto de Nanociencia y Materiales de Aragon, Universidad de Zaragoza, Spain. The synthesis of materials has been performed by the Platform of Production of Biomaterials and Nanoparticles of the NANBIOSIS ICTS, more specifically by the Nanoparticle Synthesis Unit of the CIBER in BioEngineering, Biomaterials & Nanomedicine (CIBER-BBN). J. B.-A. acknowledges the Spanish Government for an FPU predoctoral contract. M. E. acknowledges the Diputacion General de Aragon (DGA) for a predoctoral contract. The authors thank Dr Javier Calzada and Dr Silvia Irusta for their help with UPLC and XPS data acquisition. E. P. U. thanks Gobierno de Aragón-FSE (Spain, grupo Aminoácidos y Péptidos, E19_20R) for funding.

Chapter 9., The present chapter overviews the role of iron-based nanoparticles as enzyme-mimicking surrogates and their potential role in tumor microenvironments. The unique and challenging chemical features surrounding the tumor environment make necessary the development of robust and versatile catalytic platforms. Fe-based catalysts can selectively induce a series of adverse reactions for minimizing cancer cell’s proliferation and survival. Recently, the development of inorganic nanomaterials with enzyme-like properties that can outperform or complement the role of natural enzymes is being the subject of intense research. Herein, we highlight the relevance of different Fe-based nanocatalysts and provide a deeper insight of the reaction mechanisms behind their unique capability to catalyze a wide variety of enzymatic reactions of interest and potential for the development of alternative cancer therapies. Furthermore, the most recent advances on single-atom catalysts have been also summarized and highlighted.

The present work sheds light on a generally overlooked issue in the emerging field of bio-orthogonal catalysis within tumor microenvironments (TMEs): the interplay between homogeneous and heterogeneous catalytic processes. In most cases, previous works dealing with nanoparticle-based catalysis in the TME, focus on the effects obtained (e.g. tumor cell death) and attribute the results to heterogeneous processes alone. The specific mechanisms are rarely substantiated and, furthermore, the possibility of a significant contribution of homogeneous processes by leached species –and the complexes that they may form with biomolecules- is neither contemplated nor pursued. Herein, we have designed a bimetallic catalyst nanoparticle containing Cu and Fe species and we have been able to describe the whole picture in a more complex scenario where both homogeneous and heterogeneous processes are coupled and fostered under TME relevant chemical conditions. We investigate the preferential leaching of Cu ions in the presence of a TME overexpressed biomolecule such as glutathione (GSH). We demonstrate that these homogeneous processes initiated by the released by Cu-GSH interactions are in fact responsible for the greater part of the cell death effects found (GSH, a scavenger of reactive oxygen species is depleted and highly active superoxide anions are generated in the same catalytic cycle). The remaining solid CuFe nanoparticle becomes an active catalase-mimicking surrogate able to supply oxygen from oxygen reduced species, such as superoxide anions (by-product from GSH oxidation) and hydrogen peroxide, another species that is enriched in the TME. This enzyme-like activity is essential to sustain the homogeneous catalytic cycle in the oxygen-deprived tumor microenvironment. The combined heterogeneous-homogeneous mechanisms revealed themselves as highly efficient in selectively killing cancer cells, due to their higher GSH levels compared to healthy cell lines.

Plasmonic photocatalysts combining metallic nanoparticles and semiconductors have been aimed as versatile alternatives to drive light-assisted catalytic chemical reactions beyond the ultraviolet (UV) regions, and overcome one of the major drawbacks of the most exploited photocatalysts (TiO2 or ZnO). The strong size and morphology dependence of metallic nanostructures to tune their visible to near-infrared (vis-NIR) light harvesting capabilities has been combined with the design of a wide variety of architectures for the semiconductor supports to promote the selective activity of specific crystallographic facets. The search for efficient heterojunctions has been subjected to numerous studies, especially those involving gold nanostructures and titania semiconductors. In the present review, we paid special attention to the most recent advances in the design of gold-semiconductor hetero-nanostructures including emerging metal oxides such as cerium oxide or copper oxide (CeO2 or Cu2O) or metal chalcogenides such as copper sulfide or cadmium sulfides (CuS or CdS). These alternative hybrid materials were thoroughly built in past years to target research fields of strong impact, such as solar energy conversion, water splitting, environmental chemistry, or nanomedicine. Herein, we evaluate the influence of tuning the morphologies of the plasmonic gold nanostructures or the semiconductor interacting structures, and how these variations in geometry, either individual or combined, have a significant influence on the final photocatalytic performance.

This article belongs to the Special Issue State of the Art and Future Trends in Nanostructured Biocatalysis., The transformation of glucose represents a topic of great interest at different levels. In the first place, glucose is currently conceived as a green feedstock for the sustainable production of chemicals. Secondly, the depletion of glucose at the cellular level is currently envisioned as a promising strategy to treat and alter the erratic metabolism of tumoral cells. The use of natural enzymes offers multiple advantages in terms of specificity towards the glucose substrate but may lack sufficient robustness and recyclability beyond the optimal operating conditions of these natural systems. In the present work, we have evaluated the potential use of an inorganic based nanohybrid containing gold nanoparticles supported onto ordered mesoporous supports. We have performed different assays that corroborate the enzyme-mimicking response of these inorganic surrogates towards the selective conversion of glucose into gluconic acid and hydrogen peroxide. Moreover, we conclude that these enzyme-like mimicking surrogates can operate at different pH ranges and under mild reaction conditions, can be recycled multiple times and maintain excellent catalytic response in comparison with other gold-based catalysts., Financial support from the European Research Council (ERC Advanced Grant CADENCE number 742684) is gratefully acknowledged. The TEM measurements were conducted at the Laboratorio de Microscopias Avanzadas, Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Spain. The synthesis of materials has been performed by the Platform of Production of Biomaterials and Nanoparticles of the NANOBIOSIS ICTS, more specifically by the Nanoparticle Synthesis Unit of the CIBER in BioEngineering, Biomaterials & Nanomedicine (CIBER-BBN). J.B-A. acknowledges the Spanish Government for an FPU predoctoral contract.